Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)

NCT ID: NCT04874909

Last Updated: 2022-10-31

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-08
• Study Completion Date: 2024-11-30

Brief Summary

The purpose of the C'IL-LICO RICM study is to develop innovative and transformative diagnostic and prognostic for patients suffering from ciliopathies leading to renal failure.

The objectives is to decipher disease mechanisms and highlight signaling pathways altered in at-risk to develop renal failure patient groups and to produce a prognostic biomarker-based kit to predict the evolution of ciliopathy patients towards renal impairment.

Detailed Description

Ciliopathies are a large group of rare and severe genetic diseases caused by ciliary dysfunction, in which nearly all organs can be affected. In spite of being individually rare, they affect collectively up to one per 2000 people. Over the past two decades, more than 90 genes have been reported as mutated in ciliopathy patients. Most proteins encoded by these genes play key roles in the biogenesis or function of cilia, in which they define different functional subdomains. Genetic analyses of ciliopathies revealed a vast clinical variability and a broad genetic heterogeneity as: 1) mutations of the same disease-causing gene can result in distinct clinical entities and, conversely, 2) mutations in several independent genes can lead to similar clinical features, implying both phenotypic and genetic overlaps. The extent and severity of organ involvement may be correlated in part with the nature or location of the mutational event, the cell/tissue specific expression and effect of the mutated protein on cilia dysfunction.

Renal involvement is one of the most frequent manifestations in ciliopathies, and it leads to excessive morbidity and mortality. This includes renal cystic dysplasia (RCD), a kidney developmental defect, and nephronophthisis (NPHP), a chronic tubulointerstitial nephritis, both disorders representing frequent causes of end-stage renal disease (ESRD) during childhood to early adulthood. This makes ESRD a terminal endpoint of either isolated or syndromic ciliopathies, with, hitherto, no available curative treatment of chronic kidney disease whatsoever. The only bearable option is renal transplantation. As the average life-span of a functioning kidney transplant is about 10-15 years, it is urgent to identify therapeutic solutions that slow down progression of CKD in ciliopathies, and delay or avoid dialysis or transplantation. Today, the diagnosis of ciliopathies is first based on primary clinical manifestations, and then confirmed by gene mutation identification. However, even in patients with identified causative mutations, it is impossible to predict the severity of the disease, the risk of appearance (if not present at diagnosis), and/or the rate of progression of CKD. Thus, a crucial issue in the field of ciliopathies is to be able to perform early detection of at-risk patients prior to development of CKD as well as to predict disease progression rate.

Conditions

Ciliopathies; Nephronophthisis; Senior-Loken Syndrome; Joubert Syndrome; Jeune Syndrome; Bardet-Biedl Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

"Case" Patient

Patient with ciliopathy

Group Type: OTHER

Blood sample

Intervention Type: OTHER

Blood sample of 15ml max by subject (case, related individual, control) once time:

• subject less than 5 kg : 1.8 to 4.5 ml max
• subject 5 kg to 10 kg : 4.5 to 9 ml max
• subject 10 kg to 15 kg : 9 to 13.5 ml
• subject 15 kg to 20 kg : 13.5 to 15 ml max

Urine sample

Intervention Type: OTHER

Urine sample (500 ml) once time

Healthy related individual

Individual without ciliopathy but related to a patient with ciliopathy (father, mother, brother, sister)

Group Type: OTHER

Blood sample

Intervention Type: OTHER

Blood sample of 15ml max by subject (case, related individual, control) once time:

• subject less than 5 kg : 1.8 to 4.5 ml max
• subject 5 kg to 10 kg : 4.5 to 9 ml max
• subject 10 kg to 15 kg : 9 to 13.5 ml
• subject 15 kg to 20 kg : 13.5 to 15 ml max

Urine sample

Intervention Type: OTHER

Urine sample (500 ml) once time

"Negative Control" patient

patient without renal disease

Group Type: OTHER

Blood sample

Intervention Type: OTHER

Blood sample of 15ml max by subject (case, related individual, control) once time:

• subject less than 5 kg : 1.8 to 4.5 ml max
• subject 5 kg to 10 kg : 4.5 to 9 ml max
• subject 10 kg to 15 kg : 9 to 13.5 ml
• subject 15 kg to 20 kg : 13.5 to 15 ml max

Urine sample

Intervention Type: OTHER

Urine sample (500 ml) once time

"Positive Control" patient

patient with renal disease other that ciliopathy but with a similar renal function to the ciliopathy group ("case" patient)

Group Type: OTHER

Blood sample

Intervention Type: OTHER

Blood sample of 15ml max by subject (case, related individual, control) once time:

• subject less than 5 kg : 1.8 to 4.5 ml max
• subject 5 kg to 10 kg : 4.5 to 9 ml max
• subject 10 kg to 15 kg : 9 to 13.5 ml
• subject 15 kg to 20 kg : 13.5 to 15 ml max

Urine sample

Intervention Type: OTHER

Urine sample (500 ml) once time

Interventions

Blood sample

Blood sample of 15ml max by subject (case, related individual, control) once time:

• subject less than 5 kg : 1.8 to 4.5 ml max
• subject 5 kg to 10 kg : 4.5 to 9 ml max
• subject 10 kg to 15 kg : 9 to 13.5 ml
• subject 15 kg to 20 kg : 13.5 to 15 ml max

Intervention Type: OTHER

Urine sample

Urine sample (500 ml) once time

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

"Case" Patient :

• with nephronophthisis or ciliopathy with known genetic diagnosis or not
• signed the Informed consent form (patient or legal guardians if minor/incapable major)
• no limit of age, this patients could be recruited from the birth
• social insurance affiliation

Healthy related individual :

• related with a included patient (father, mother, brother, sister)
• signed the Informed consent form (major or legal guardians if minor/incapable major)
• no limit of age, this patients could be recruited from the birth
• social insurance affiliation

"Negative Control" patient :

• without chronic renal failure
• signed the Informed consent form (major or legal guardians if minor/incapable major)
• no limit of age, this patients could be recruited from the birth
• social insurance affiliation

"Positive Control" patient :

• with chronic renal failure not related with a ciliary dysfunction
• signed the Informed consent form (major or legal guardians if minor/incapable major)
• no limit of age, this patients could be recruited from the birth
• social insurance affiliation

Exclusion Criteria

• pregnant, parturious and nursing mothers.
• with functional renal graft
• use an experimental treatment during 30 days before inclusion date

Healthy related individual :

• pregnant, parturious and nursing mothers.

"Negative Control" patient :

• pregnant, parturious and nursing mothers.

"Positive Control" patient :

• pregnant, parturious and nursing mothers.
• with functional renal graft
• use an experimental treatment during 30 days before inclusion date

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sophie SAUNIER, PhD

Role: STUDY_CHAIR

Imagine Institute

Locations

Hôpital Necker-Enfants Malades

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Stanislas LYONNET, MD, PhD

Role: CONTACT

stanislas.lyonnet@aphp.fr

(33) 1 42 75 49 96

Sandra COLAS

Role: CONTACT

sandra.colas@aphp.fr

+33 1 71 19 64 32

Facility Contacts

Stanislas LYONNET, MD, PhD

Role: primary

stanislas.lyonnet@aphp.fr

(33) 1 42 75 49 96

Other Identifiers

ID-RCB Number

Identifier Type: OTHER

Identifier Source: secondary_id

APHP200896

Identifier Type: -

Identifier Source: org_study_id